BIOCHEMISTRY

2017 Dr. Đặng Thanh Dũng

The life is divided into 5 kingdoms

Khởi sinh Nguyên sinh Thực vật Nấm Động vật

(1-3 µm)
The life is divided into 5 kingdoms

Diverse living organisms share common chemical features.

Biochemistry?

- Basic principle of biochemistry is the study of the chemical processes which occur
in living matter.

- Foundation of biochemistry: Cellular foundations, chemical foundations, physical

foundations, genetic foundations and evolutionary foundations.
Biochemists in the past

Karl Scheele: Swedish founder of biochemistry. He studied the

chemical composition of matter in the mid 1700.

Walter Flemming: discovered chromosomes in 1875

Hans Kreb: proposed the Kreb cycle of the TCA in 1937

James Watson & Francis Crick: described the double helical

structure of DNA in 1953

Biochemists in the past

Edward & Hans Buchner: found that extracts from yeasts could

bring about fermentation of sugar into ethanol in 1897

Paul Boyer and J. Walker: discovered mechanism to generate

ATP in 1997

Danish J. Skou: studied the pump that drives sodium and

potassium across the membranes

Stanley Prusiner: discovered the organism that caused “mad

cow disease”
1.1 Cellular foundations
1.1. Cellular foundations
Cells

Cells are the structural and

functional units of all living
organisms
Biochemistry in cell
Eukaryote & Prokaryote
Source of energy

Organisms can be classified according to their source of energy (sunlight or oxidizable

chemical compounds) and their source of carbon for the synthesis of cellular material.
The organic compounds from
which most cellular materials
are constructed
Structural hierarchy in the molecular
organization of cells.
Cellular foundations: summary

•All cells are bounded by a plasma membrane; have a cytosol containing

metabolites, coenzymes, inorganic ions, and enzymes; and have a set of genes
contained within a nucleoid (prokaryotes) or nucleus (eukaryotes).

•Phototrophs use sunlight to do work; chemotrophs oxidize fuels, passing electrons

to good electron acceptors: inorganic compounds, organic compounds, or molecular
oxygen.

•Bacterial cells contain cytosol, a nucleoid, and plasmids. Eukaryotic cells have a
nucleus and are multicompartmented, segregating certain processes in specific
organelles, which can be separated and studied in isolation.

•Cytoskeletal proteins assemble into long filaments that give cells shape and rigidity
and serve as rails along which cellular organelles move throughout the cell.

•Supramolecular complexes are held together by noncovalent interactions and form

a hierarchy (level) of structures, some visible with the light microscope. When
individual molecules are removed from these complexes to be studied in vitro,
interactions important in the living cell may be lost.
1.2. Chemical foundations
Elements essential to animal life and health

Bulk elements (shaded orange) are structural components of cells and tissues
and are required in the diet in gram quantities daily. For trace elements (shaded
bright yellow), the requirements are much smaller: for humans, a few milligrams
per day of Fe, Cu, and Zn, even less of the others. The elemental requirements
for plants and microorganisms are similar to those shown here; the ways in
which they acquire these elements vary.
Some common functional groups of biomolecules.
Một số nhóm phổ biến của phân tử chức năng sinh học

Acetyl coenzyme A or acetyl-CoA tham gia trong nhiều phản ứng sinh hóa
trong protein, carbohydrate và lipid. Chức năng chính của nó là chuyển
nhóm acetyl vào chu trình citric acid để được oxi hóa tạo sản phẩm năng
lượng.
Representations of molecules.

Perspective Ball-and-stick
form model

Alanine
Space-filling model
(van der Walls radius)

Three ways to represent the structure of the amino acid alanine.

Configurations of geometric isomers

In the vertebrate retina, the initial event in light detection is the absorption of
visible light by 11-cis-retinal. The energy of the absorbed light (about 250 kJ/mol)
converts 11-cis-retinal to all-trans-retinal, triggering electrical changes in the retinal
cell that lead to a nerve impulse.
Complementary fit between a macromolecule and a
small molecule

- Substrate & enzyme

-Hormone & receptor on cell
membrane
- Antigen & antibody
Chemical foundations: summary

A nearly universal set of several hundred small molecules is found in living cells; the
interconversions of these molecules in the central metabolic pathways have been
conserved in evolution.

Proteins and nucleic acids are linear polymers of simple monomeric subunits; their
sequences contain the information that gives each molecule its three-dimensional
structure and its biological functions.

Molecular configuration can be changed only by breaking covalent bonds. For a

carbon atom with four different substituents (a chiral carbon), the substituent groups
can be arranged in two different ways, generating stereoisomers with distinct
properties. Only one stereoisomer is biologically active.

Interactions between biological molecules are almost invariably stereo specific: they
require a complementary match between the interacting molecules.
1.3. Physical foundations
Organisms transform energy and matter from
their surroundings
Living organisms derive energy from their surroundings in two ways:

(1) they take up chemical fuels (such as glucose) from the environment and extract
energy by oxidizing them

(2) they absorb energy from sunlight.

Energy Coupling Links Reactions in Biology

DG > 0 ---> nonspontaneous process (endergonic)

DG < 0 ---> spontaneous process (exergonic)
DG = 0 ---> equilibrium (DGo = - RT ln Keq)
The central role of ATP in
metabolism
The central role of ATP in
metabolism

Metabolism Is Regulated to
Achieve Balance
and Economy

Feedback inhibition
Living cells are open systems, exchanging matter and energy with their
surroundings, extracting and channeling energy to maintain themselves in a
dynamic steady state distant from equilibrium.

Energy is obtained from sunlight or fuels by converting the energy from electron
flow into the chemical bonds of ATP. The tendency for a chemical reaction to
proceed toward equilibrium can be expressed as the free-energy change.

When ΔG of a reaction is negative, the reaction is exergonic and tends to go

toward completion; when ΔG is positive, the reaction is endergonic and tends to
go in the reverse direction. When two reactions can be summed to yield a third
reaction, the Δ G for this overall reaction is the sum of the ΔGs of the two
separate reactions. This provides a way to couple reactions.

The conversion of ATP to Pi and ADP is highly exergonic (large negative Δ G),
and many endergonic cellular reactions are driven by coupling them, through a
common intermediate to this reaction.

The catalytic activity of enzymes in cells is regulated.

Metabolism is the sum of many interconnected reaction sequences that

interconvert cellular metabolites. Each sequence is regulated so as to provide
what the cell needs at a given time and to expend energy only when necessary
1.4. Genetic foundations
The Structure of DNA Allows for Its Replication
and Repair with Near-Perfect Fidelity

A: deoxyadenylate
G: deoxyguanylate
C: deoxycytidylate
T: deoxythymidylate
DNA to RNA to protein

Linear sequences of deoxyribonucleotides

in DNA, arranged into units known as
genes, are transcribed into ribonucleic acid
(RNA) molecules with complementary
ribonucleotide sequences. The RNA
sequences are then translated into
linear protein chains, which fold into their
native three-dimensional
shapes, often aided by molecular
chaperones. Individual proteins commonly
associate with other proteins to form
supramolecular complexes, stabilized by
numerous weak interactions.
Genetic information is encoded in the linear sequence of four
deoxyribonucleotides in DNA.

The double-helical DNA molecule contains an internal template for its own
replication and repair.

The linear sequence of amino acids in a protein, which is encoded in the

DNA of the gene for that protein, produces a protein’s unique three-
dimensional structure.

Individual macromolecules with specific affinity for other macromolecules

self-assemble into supramolecular complexes.
1.4. Evolutionary foundations
Role of mutation in evolution
Role of mutation in evolution

Mutation can kill the cell but sometime

the cell can survive to a new
enviroment because of mutation
Evolution of eukaryotes through endosymbiosis.
A possible “RNA world” scenario
Landmarks of evolution of life on earth
Summary

Occasional inheritable mutations yield an organism that is better suited for

survival in an ecological niche and progeny that are preferentially selected. This
process of mutation and selection is the basis for the Darwinian evolution that
led from the first cell to all the organisms that now exist, and it explains the
fundamental similarity of all living organisms.

Life originated about 3.5 billion years ago, most likely with the formation of a
membrane-enclosed compartment containing a self-replicating RNA molecule.
The components for the first cell were produced by the action of lightning and
high temperature on simple atmospheric molecules such as CO2 and NH3.

The catalytic and genetic roles of the early RNA genome were separated over
time, with DNA becoming the genomic material and proteins the major catalytic
species.
Summary

Eukaryotic cells acquired the capacity for photosynthesis and for

oxidative phosphorylation from endosymbiotic bacteria. In multicellular
organisms, differentiated cell types specialize in one or more of the
functions essential to the organism’s survival.

Knowledge of the complete genomic nucleotide sequences of

organisms from different branches of the phylogenetic tree provides
insights into the evolution and function of extant organisms and offers
great opportunities in human medicine.